This invention relates to the generation of a time-modulated electrospray. Electrosprays are useful for analyzing solutes in a sample solution. More particularly the present invention provides a method and apparatus for intermittently forming an electrospray from a sample solution which is subsequently analyzed.
A liquid flowing through a capillary jet or orifice may be converted to a spray of small charged droplets (of the order of 1 .mu.m in diameter) by applying a strong electric field to the liquid as it emerges from the tip of the capillary. For sufficiently high applied field, the electrostatic stress imposed by the field and the surface-induced electrical charge is sufficient to overcome the surface tension forces on the liquid. Breaking apart into a large number of small charged droplets is a way for the liquid to disperse the charge and reach a lower total energy state. This process of forming a spray is commonly known as electrospray.
Previous applications of the electrospray process to mass spectrometry regard electrospray as a steady-state process. The applied electric field referred to above is kept constant in time and, as a result, spray formation is constant in time. In a recent abstract on coupling electrospray to a time-of-flight mass spectrometer, Whitehouse, et al state that electrospray is an inherently DC phenomenon, requiring the continuous presence of a strong potential gradient about a sharp needle tip to form charged droplets, "Electrospray ionization on an ion storage time-of-flight mass spectrometer" J. G. Boyle et al, extended abstracts from the 12th International Mass Spectrometry Conference, Aug. 26-30, 1991 in Amsterdam, Holland, abstract #WeM-DO4 on p. 238.
At the present time apparatus are available for forming an electrospray of a sample solution such as a liquid stream effluent from a liquid chromatography separation step and subsequently analyzing the electrospray with a mass analyzer such as a quadrupole mass spectrometer, an ion trap, a time-of-flight mass spectrometer or a magnetic sector mass spectrometer or the like. In any kind of mass spectrometer (MS) manipulation of analysis that requires a finite time to accomplish or in which ions need to be stored whether prior to or as part of the analysis, such as in a time-of-flight mass spectrometer, a quadrupole ion trap, many implementations of MS/MS, or a Fourier Transform mass spectrometer, a non-continuous source of the electrospray can provide increased efficiency of analysis. Thus, for example in the case of an ion trap, ions are accumulated and stored in a small volume by appropriate electric fields. The mass-to-charge spectrum of these accumulated ions cannot be ascertained until the trap is "swept clean", i.e., voltages are applied to the trap that sequentially cause ions to be ejected and detected. It is only by virtue of the parameters that cause their ejection that their mass-to-charge ratio is known. During this readout interval, newly formed electrospray ions cannot efficiently be introduced into the trap, thus, they are wasted. Similarly, a the-of-flight mass spectrometer analyzes ions of different mass-to-charge ratio, by releasing or creating a burst of ions of a given energy, and then measuring the differences in their mass-to-charge ratio on the basis of their differing transit times along some predetermined trajectory. Newly created ions cannot be introduced during this transit period without potentially confusing the analysis. Thus, new ions generated during this transit time are wasted.
In most prior electrospray sources, the electrospray capillary must be maintained at a high electrical potential with respect to ground if the mass-to-charge analyzer and its vacuum housing are to be kept close to ground potential. This means that any means to introduce liquid to the electrospray source such as a liquid chromatograph or pump, must either also be maintained at a high electrical potential with respect to ground, or must be connected to the electrospray capillary by long lengths of narrow bore insulating tubing. This can compromise system performance as well as present something of a safety hazard.
In a liquid chromatograph, a stream of solvent, containing a mixture of chemical species in solution, is passed at elevated pressure through a chromatographic column. The column is so designed that it separates the mixture, by differential retention on the column, into its component species. The different species then emerge from the column as distinct bands in the solvent stream, separated in time. The liquid chromatograph provides therefore, an ideal device for the introduction into a mass spectrometer of single species, separated from initially complex mixtures.
It has been proposed in U.S. Pat. No. 4,545,293 to use a strong gas flow to entrain ions and droplets through a capillary composed of an insulator such that they migrate against the opposing electric field across that capillary, i.e., the viscous drag of the gas flow on these ions or droplets present is larger than the electrostatic force on the ions. A specific benefit of this arrangement is that it can allow the capillary, from which the electrospray emanates, and the mass analyzer to be maintained at relatively arbitrary electrical potentials, or most conveniently, they may be both at ground. In this system, however, charged droplets and ions may deposit on the inner wall of this insulated capillary. This charge then may leak away at an indeterminate rate which may affect interface stability.
Accordingly, it would be desirable to provide a method and apparatus for modulating the conversion of a liquid sample into a form such as an electrospray which permits subsequent analysis in a mass spectrometer or the like. In addition, it would be desirable to provide such an apparatus wherein the liquid sample can be converted to an electrospray and both apparatus for producing the electrospray and the electrospray analysis apparatus can be maintained at close to ground electrical potential. Such a method and apparatus would minimize sample waste and would provide a safe and efficient means for analyzing the sample.